Teeth are colonized by bacteria which initiate a host response. This host response can ultimately lead to the destruction of periodontal tissues. The goal of this proposal is to study the in vivo production of selected cytokines and metalloproteinases in periodontal tissue destruction. An animal model will be utilized because these experiments cannot carried out in humans or in vitro. Immunohistochemistry, in situ hybridization and reverse transcription polymerase chain reaction (RT-PCR) experiments will examine the production of selected cytokines and metalloproteinases that may be antecedents to localized alveolar bone loss. We will determine if there is tissue specific expression of these molecules in gingival connective tissue, periodontal ligament and alveolar bone. The cellular origin of these potent molecules will also be unambiguously established. These studies are likely to be significant since it is not known whether specific cytokines or metalloproteinases are produced in association with localized alveolar bone loss. Pharmacologic intervention with IL-I receptor antagonist will determine whether localized alveolar bone loss is IL-I dependent. Furthermore, we will examine the effect . of this IL-I blocker on leukocyte recruitment and the pattern of cytokine and metalloproteinase expression. These proposed experiments should define the cellular events associated with localized alveolar bone loss and identify the events that are IL-I dependent. Ultimately studies such as these should make it feasible to develop strategies for pharmacologic intervention in the host-response leading to periodontal tissue destruction.